info@auctorespublishing.com
+1-(302)-520-2644
+1-(302)-520-2644

Tripartite Mechanism of Neural Memory: Proof-of-Concept with Neuromimetic Impedence Electrodes

  1. Home
  2. Journals
  3. Biomedical Research and Clinical Reviews
  4. Archives
Submit Guidelines

Review Article | DOI: https://doi.org/10.31579/2692-9406/021

Tripartite Mechanism of Neural Memory: Proof-of-Concept with Neuromimetic Impedence Electrodes

  • Gerard Marx 1*
  • Chaim Gilon 2

*Corresponding Author: Gerard Marx, Biotech Ltd., Jerusalem, Israel.

Citation: G Marx, C Gilon. (2020) Tripartite Mechanism of Neural Memory:Proof-of-Concept with Neuromimetic Impedance Electrodes.Biomedical Research and Clinical Reviews. 1(3); DOI: 10.31579/2692-9406/021

Copyright: © 2020 Gerard Marx, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 31 August 2020 | Accepted: 08 September 2020 | Published: 11 September 2020

Keywords: neuromimetic electrode; impedence; chemodynamic sensing; trace metals; neurotransmitters; memory

Abstract

The idea that neural signaling is the basis of mental processes has a long history. We graphically summarize salient developments in the neurobiology of signaling, as a Timeline. In particular, we review the “tripartite mechanism” of neural memory, which centers on the interactions between a neuron with its surrounding extracellular matrix (nECM) doped with metals and neurotransmitters (NTs). Essentially, the neuron employs the nECM as its “memory material”, wherein it uses dopants to encode cognitive units of information (termed “cuinfo”). The NTs, which elicit bodily reactions (feelings), also encode past feelings as emotions, which “color” mental states in real-time and in memory.

In the interest of developing experimental tests of the tripartite mechanism, impedance glass electrodes were covalently coated with an exemplar NT (oxytocin) or a sulfated tetra-saccharide analog of the nECM, were constructed and tested. The two types of coated, neuro-mimetic electrodes, termed “neulectrodes”, were capable of detecting metals, such as Hg+2, Pb+2, Cd+2, Cu+2, and Zn+2 with very high selectivity and sensitivity. The “neulectrodes” demonstrated that the chemodynamic interactions of metal cations with NTs or nECM-saccharide analogues can translate into electrodynamic signals. They experimentally validate the concept of the tripartite mechanism that underlies the chemo-electric encoding of neural memory.

Background

Neurons are chemo- and electro-dynamically linked cells that express a talent of mentation and somehow encode cognitive information as the basis for neural memory. But details are lacking regarding the physicality of the neural code and where the memory trace (engram) is located. Many presume that memory is somehow stored in the synaptic gaps between neurons (Cajal, 1911; Hebbs, 1949 ; Kandel et al, 2013; Cizeron et al, 2020), though this seems questionable from the point of view of persistence and theoretic credibility (Arshavsky 2006; Gallistel & King  2009; Amit 2013; Marx & Gilon, 2012-2020).

Some researchers developed nano- or microdevices to enable simultaneous, long-term, multi-site, intracellular electrical recordings from single or many neurons (Spira & Hai, 2013). While they explored the electrophysiologic aspects of synaptic signaling using sensing electrodes, they did not address the issue of the mental states achieved by neurons. Other workers suggested that memory is stored in the nucleus (Kandel, 2001; Josselyn & Frankland, 2015), though the kinetics of nuclear processes appear to be too slow and require high energy.

The computer metaphor for neural memory exerts a strong influence on the field of cognitive neurobiology. Many see a direct parallel between a computer and the brain (Turing, 1943; McCulloch & Pitts, 1943; von Neumann, 1958; Arbib, 1987, 2000; Piccinini G. 2006; Giudolin et al, 2011).

 “Computational systems are useful to describe brain processes mathematically”.  -  Giudolin et al, 2011

But the metaphor is incomplete. Aside from the quite different energy expenditures by a brain compared to a supercomputer (i.e. 20 Watts vs 250 megaWatts), it does not account for emotive states achieved by neural systems, for which there are no digital or electrodynamic equivalents.

The idea of neural signaling as the basis of mental processes has a long history beginning with Galvani through Golgi, Cajal, Hebb and Kandel, as we  graphically summarize in the Timeline presented below (Figure 1).

Figure  1. Milestones in the Timeline of neurobiology, acknowledging key contributors to unravelling the electrical and chemical modes of neural signaling. The Timeline (based on reviews: Kandel & Squire, 2000; Langmoen & Apuzzo, 2007; and our own work) emphasizes the parallel development of two dynamics of neural signaling: the electrical mode and the chemical mode.

Subsequent to the observations of Cajal of synaptic contacts between neurons (Cajal, 1911), a singular contribution to the electrical mode of was the McCulloch–Pitts mathematical model of a lone neuron (McCulloch & Pitts, 1943). This approach was subsequently amplified by the concepts of electrical signaling expressed as “synaptic plasticity” and “long term potentiation”.

The chemical mode took longer to develop, buttressed by the eventual confirmation of Golgi’s observation of a perineural net (PNN), identified as a web of glycosaminoglycans (GAGs) around the neurons, now termed “nECM”.  The discovery of peptidic neurotransmitters (NTs) and their receptors also enabled a chemodynamic view of neural net communication. But signaling by itself does not resolve the core enigma of how neurons can remember existential events.

How is an emotive mental state encoded, stored and recalled from memory?

1.1. Tripartite mechanism of neural memory

We have proposed a tripartite mechanism for neural memory based on the formation of metal-centered complexes that attract neurotransmitters (NTs) (Marx & Gilon, 2012-2019). Neurotransmitters (NTs) elicit psychic states parallel to physiologic reactions. Chemically, NTs bind to the metals anchored in the nECM. Effectively, they combine to establish the neuron’s code for emotive states (Figure 2).

Figure 2. Icons of an electron-rich nECM metal-confinement “address”, capable of complexing with metals and neurotransmitters (NTs), thereby encoding a cognitive unit of information (cuinfo). Each NT endows the cuinfo (singular & plural) with an emotive quality not available in binary code.

To encapsulate: The “neuron” marshals the components available to it, notably the surrounding extracellular matrix (nECM) and the dopants (metals and NTs) which the neuron accumulates within vesicles.  The neuron employs these to encode cognitive units of information, called “cuinfo”, metal-centered complexes within the nECM, described by a chemographic notation (Figure 2). This mechanism is universal, in that it applies to the recall function of all neural creatures, from C. elegans (302 neurons) to homo sapien (1015 neurons).

 The term “chemotronic” refers to an intersection disciplines, such as those of chemistry with electronics or optics (see Khrustalev & Rozhitskii, 2001). Here, we propose that memory links biochemical processes to psychological states (i.e. emotions). For example, hydrogels have been studied as structural entities, in terms of shear thinning, stretching, self-healing and breaking strength. (Zhang & Khadehosseini, 2017), but have not been studied for “chemotronic” signaling potential for encoding “psycho-chemical” states.

In this regard, consider the nECM as a 3-D hydrogel comprising a lattice of sulfated glycosamino-glycans (GAGs) (such as hyaluronate, chondroitins and heparans) which bind metal cations. The degree of sulfation of the GAG’s is a major factor impinging on its metal binding affinity. Though a number of sulfation-enzymes have been identified (Gamma et al, 2006; Soares, 2016; Malaeb et al, 2019), correlation between the neuro-saccharide sulfation pattern and metal-binding characteristics remains obscure. Thus, experimental evaluation of the metal-binding affinities of specifically sulfated saccharides remains a goal of material scientists, which may incidentally clarify the signaling properties of neurons interacting with their nECM.

2. Results and Discussion

Following the idea of McCulloch & Pitts (Figure 1) that described a single neutron in mathematical terms, we propose that the impedence electrode is a model for a chemo-electric neural receptor. Inspired by these ideas, our colleagues embarked on a program to fabricate various neuro-mimetic impedence electrodes (“neulectrodes”) coated with materials available to the neuron, namely a neurotransmitter (oxytocin) or a sulfated tetrasaccharide analogue of the nECM. These electrodes could be tested for their binding affinity and selectivity to different metal cations.

We review two published examples that use Electrochemical Impedance Spectroscopy (EIS) as a method to detect changes in the electrochemical properties of coatings of “tripartite” components. We call such neuromimetic electrodes, “neulectrodes”. EIS is highly sensitive to interactions of the electrode sensing layer with analytes, especially to conformational changes that result from metal binding to the surface. It does not depend on fluorescence, luminescence or light  absorbance techniques frequently used to study metal binding by biopolymers.

2.1. “Neulectrode” type 1: NT-coated impedance sensor

An impedence electrode was modified in step-wise manner to covalently coat the sensing surface with oxytocin (OT), as schematically illustrated in Figure 3.

Figure 3. A schematic outline of the preparation of the oxytocin (OT) -coated EIS electrode. (The preparation details are described in Tadi et al, 2017).The OT-coated electrode was particularly sensitive (~10-12 M) to Cu+2 and Zn+2, but showed very low responsiveness to other metal cations (Pb+2, Mg+2, Cd+2, Ni+2, Ca+2, Fe+3, Ag+ and K+) (Tadi et al, 2017). These results were in accord with other reports that oxytocin has great affinity for metals, which are cofactors in its physiologic effects (Neumann, 2007; Wyttenbach et al, 2008; van der Burg et al, 2009; Liu et al, 2005).

Each neural sensor has a unique specificity for a given NT ligand (Neumann, 2007). Thus, the OT-coated electrode, could be described as “neuro-mimetic” and might become diagnostically useful in a clinical setting to test for trace Cu+2 and Zn+2  in the  circulating blood or lymph fluid of patients with multiple sclerosis, Alzheimer disorder, Parkinson disorder and  autism.

2.2. “Neulectrode” type 2: Sulfated oligo-Saccharide coated impedance sensor

Uniquely sulfated tetra-saccharides were prepared (Table 1) and used to coat the EIS electrode

Surface to form the tetra-hyaluron glass, coated electrode (HA4-GCE) for testing for sensitivity to metal cations. (Alshanski et al. 2019) The hyluron tetra-saccharides (galactosamine N-Ac – Glucuronic acid; (GlcNAc–GlcA)2), were prepared as analogues of hyaluron (HA), a major polymeric component of the nECM (Rother et al, 2016; Yoon, 2016). While hyaluron is not generally sulfated, its tetra-saccharides serves as a good analogue of the generally sulfated chondroitins (glucosamine N-Ac-Glucuronic acid; GluNAc-GlcA)n (n≥ 2). The process for covalently coating the electrode with the tetra-hyluron azides (Table 1) was similar to that developed for oxytocin (Figure 2), using tetra-hyluron azides instead of oxytocin azide

(Alshanski et al, 2019).

Table 1: The sulfated tetra-saccharides used to coat the “neulectrode” type 2 (Alshanski et al. 2019)
Figure 4. Response of different HA4-GCE to 100 nM concentrations of Cd2+, Pb2+ and Hg2+ (N = 3). Black describes HA4-GCE, blue describes msHA4-GCE and red describes dsHA4-GCE (Alshanski et al, 2019).

The high sensitivity of the electrode coated with  sulfated HA4-GCE to metals such as Hg +2, Pb+2, and Cd+2 depended on the degree of sulfation, indicating that the interactions of sulfated oligo-saccharides with metal ions, especially heavy metal ones, are dictated by the sulfation patterns rather than by the core saccharide. Moreover, it corroborates our hypothesis that the sulfation pattern of the GAGs in the nECM determines the pattern of the metal distribution that is used for coding the neural memory.  We hypothesized that NT (like oxytocin) could form ternary complexes with the metals embedded in the sulfated GAGs in the nECM, to be used for coding emotive memory. We also hypothesized that many thousands of sensors (i.e., GPCR, K channels, receptors, integrins), presented by the neural surface serve to “read” the cognitive information encoded by the metal -NT complexes in the nECM around the neurons.

3. Conclusions

The operational details of neural memory remain the focus of intense theoretical, modeling, basic and applied research. We have proposed that cognitive information received by the neuron is encoded as metal-centered complexes in the nECM surrounding the neurons. This implies that the neuron can form defined patterns of dopant complexes (metals and NTs) in the nECM. Moreover, it is capable of chemodynamic sensing such a pattern of metal-centered complexes and translating this information into electrodynamic signaling to the neural circuit (Figure 5).

Figure 5. Conceptual model of a synthetic neuron with a variety of “neulectrodes” embedded in a lipid membrane. The sensory output of all would be directed to an electronic central processing circuit (CPU), permitting a brain-computer interface.

The “neulectrodes” are interesting from both fundamental and technological perspectives. They are truly neuro-mimetic in that they employ components available to the neuron. They may be useful as diagnostic tools or as implants for monitoring or controlling neural activity.

The two types of “neulectrodes” reviewed here demonstrate chemo-electric effects. Namely, that the chemo-dynamic interactions of metal cations with NTs or sulfated analogs of the nECM GAG can translate into electrodynamic signals. They experimentally validate the concept of the tripartite mechanism of neural memory.

4. Acknowlegement

(By GM). A memorium to my late wife and fan, the artist Georgette Batlle (1940-2009). Thanks to friends, Lilly Rivlin (New York, N.Y.) and the late Bill Needle (Eastchester, N.Y.) for their early encouragement and financial support in the period 1980-1984.

We are pleased that we inspired and instigated this work by the research groups headed by Professor Shlomo Yitzchaik and Dr. Mattan Hurevich (Hebrew University) that fabricated and studied the coated electrodes, cited and discussed here. 

5. Conflict of Interest

GM is a founder of MX Biotech Ltd., with the commercial goal to develop new classes of “memory materials” and devices.
CG is emeritus professor at the Institute of Chemistry, The Hebrew University of Jerusalem. He is active in developing technologies for the conversion of peptides and active regions of proteins into orally available drug leads.
This work did not receive any external funding support. Notwithstanding, the ideas forwarded here are scientifically genuine and presented in good faith, without commercial clouding of the concepts expressed herein. 

References

  1. Alshanski I., Blaszkiewicz J., Mervinetsky E., Rademann J., Yitzchaik S., Hurevich M. 2019.Sulfation patterns of saccharides and heavy metal ion binding.Chem. Eur. J. 25: 1 – 9
    View at Publisher | View at Google Scholar
  2. Amit, D. 2013 .Hebb vs Biochemistry: the Fundamentalist Viewpoint. In selected papers by Daniel Amit (1938-2007)
    View at Publisher | View at Google Scholar
  3. Arbib, M. A. 1987.Brains, Machines and Mathematics. 2nd Edition.Springer Verlag, New York.
    View at Publisher | View at Google Scholar
  4. Arbib, M. A. 2000.Warren McCullogh’s search for the logic of the nervous system.Perspect. Biol. Med. 43, 193-216.
    View at Publisher | View at Google Scholar
  5. Arshavsky, Y. I.  2006 ‘The seven sins’’ of the Hebbian synapse: Can the hypothesis of synaptic plasticity explain long-term memory consolidation?Progress in Neurobiology 80, 99–113.
    View at Publisher | View at Google Scholar
  6. Aschner, M. 2018.The functional significance of brain metallothioneins.FASEB J. 10, 1129-1136
    View at Publisher | View at Google Scholar
  7. Cajal R.Y. (1911).Histology of the Nervous System of Man and Vertebrates. Oxford University Press, 1995.
    View at Publisher | View at Google Scholar
  8. Cizeron, M, Qiu Z, Koniaris B, Gokhale R, Komiyama N, Fransén E, Grant S. 2020.A brainwide atlas of synapses across the mouse life span.Science 369(6501):270-275.
    View at Publisher | View at Google Scholar
  9. Gallistel, C. R., King, A. P. 2009.Memory and the Computational Brain.Wiley Blackwell, New York.
    View at Publisher | View at Google Scholar
  10. Gama C.,  Tully SE, Sotogaku N. ,  Rawat M.,  Vaidehi N.,  Goddard III W.A., Nishi A., Hsieh Wilson C. 2006.Sulfation patterns of glycosaminoglycans encode molecular recognition and activity.Nature Chemical Biology 2: 467-474.
    View at Publisher | View at Google Scholar
  11. Guidolin D., Albertin G., Guescini M., Fuxe K., Agnati L.F. 2011.Central nervous system and computation.Q. Rev. Biol. 86:265-285.
    View at Publisher | View at Google Scholar
  12. Josselyn S., Frankland P.W. 2015.Another twist in the histone memory code.Cell Research 25:151-152. doi:10.1038/cr.2014.134.
    View at Publisher | View at Google Scholar
  13. Kandel E. R., Squire L.R. (2000). Neuroscience: Breaking down scientific barriers to the study of brain and mind. Science 290: 1113-1120.
    View at Publisher | View at Google Scholar
  14. Eric R. Kandel E.R. 2001The Molecular Biology of Memory Storage: A Dialogue between Genes and Synapses Science 294: 1030-1038.
    View at Publisher | View at Google Scholar
  15. Khrustalev K.L., Rozhitskii M.M. 2001.Optochemotronics sensors-theory, experiment, practice.Proceedings of LFNM'2001. 3rd International Workshop on Laser and Fiber-Optical Networks Modeling, (Cat. No.01EX463)
    View at Publisher | View at Google Scholar
  16. Langmoen I.A., Apuzzo M.L. 2007.The brain on itself: Nobel laureates and the history of fundamental nervous system function.Neurosurgery 61: 891-907; discussion 907-908.
    View at Publisher | View at Google Scholar
  17. Liu D., Seuthe A.B., Ehrler O.T., Zhang X., Wyttenbach T., Hsu J.F., Bowers M.T. 2005.Oxytocin-receptor binding: Why divalent metals are essential.J. Am. Chem. Soc., 127: 2024-2025.
    View at Publisher | View at Google Scholar
  18. Malaeb W., Bahmad H.F., Abou-Kheir W., Mhanna R. 2019.The sulfation of biomimetic glycosaminoglycan substrates controls binding of growth factors and subsequent neural and glial cell growth.Biomater. Sci.  
    View at Publisher | View at Google Scholar
  19. Marx G., Gilon C. 2013.The molecular basis of memory. MBM Part 2: The chemistry of the tripartite mechanism.ACS Chem. Neurosci. 4, 983–993, 2013.
    View at Publisher | View at Google Scholar
  20. Marx, G., Gilon C. 2016.The molecular basis of neural memory. MBM Part 6: Chemical coding of logical and emotive modes.Int. J. Neurology Res. 2: 259-268.
    View at Publisher | View at Google Scholar
  21. Marx G., Gilon C. 2017.The molecular basis of neural memory. MBM Part 7:Artificial intelligence (AI) versus neural intelligence (NI).AIMS Medical Science, 4: 254–273
    View at Publisher | View at Google Scholar
  22. Marx G., Gilon C. 2017.Molecular basis of neural memory. Part 8.Reviewing “neuro-mimetic” technologies.Neurosci. Biomed. Engin. 5.
    View at Publisher | View at Google Scholar
  23. Marx G., Gilon C. 2018.The molecular basis of neural memory. Part. 10. The sins and redemption of neurobiology.J. Neurology Neurocrit. Care 1: 1-7.
    View at Publisher | View at Google Scholar
  24. Marx G., Gilon C. 2019.The tripartite mechanism as the basis for a biochemical memory engram J. Integr. Neurosci. 18:  23–26.
    View at Publisher | View at Google Scholar
  25. Marx G, Gilon C. 2020.Quantum considerations of neural memory.In: Quantum Boundaries of Life, Volume 82In press. Elsevier, Amsterdam.
    View at Publisher | View at Google Scholar
  26. McCulloch, W. S., Pitts W. H. 1943.A logical calculus of the ideas immanent in nervous activity. Bulletin of Mathematical Biophysics 7, 115–133.Reprinted in: McCulloch W., Embodiments of Mind, MIT Press, 1965, pp. 16–39.
    View at Publisher | View at Google Scholar
  27. Neumann I.D. 2007.Oxytocin: the neuropeptide of love reveals some of its secrets.Cell Metab. 5:231-233.
    View at Publisher | View at Google Scholar
  28. Piccinini G. 2006.Computational explanation in neuroscience.Synthese 153:343–353.
    View at Publisher | View at Google Scholar
  29. Rother S, et al. 2016Sulfated hyaluronan alters the interaction profile of TIMP-3 with the endocytic receptor LRP-1 clusters II and IV and increases the extracellular TIMP-3 level of human bone marrow stromal cells.Biomacromolecules 17:3252-3261.
    View at Publisher | View at Google Scholar
  30. Soares da Costa D., Reis R.I., Pashkuleva I. 2017.Sulfation of glycosaminoglycans and its implication in human health and disordersAnnu. Rev. Biomed. Eng. 19:1–26.
    View at Publisher | View at Google Scholar
  31. Spira M.E., Hai  A. 2013.Multi-electrode array technologies for neuroscience and cardiology.Nature Nanotechnology 8: 83-95.
    View at Publisher | View at Google Scholar
  32. Tadi K.K., Alshanski I., Mervinetsky E., Marx G.,  Petrou P., Dimitrios K.M. Gilon C., Hurevich M., Yitzchaik S. 2017.Oxytocin-monolayer-based impedimetric biosensor for zinc and copper ions.ACS Omega 2: 8770−8778.
    View at Publisher | View at Google Scholar
  33. Turing, A. 1936.On computable numbers with an application to the Entscheidungs problem.Proc. London Math. SocSeries 2, 42: 230-265.
    View at Publisher | View at Google Scholar
  34. Von Neumann, J. 1958.The Computer and the Brain.Yale University Press, New Haven CT, 3rd Ed.
    View at Publisher | View at Google Scholar
  35. Van der Burg Y.E., Palmblad M., Dalebout H., Heeren R.M., Deelder A.M. 2009.Electron capture dissociation of peptide hormone changes upon opening of the tocin ring and complexation with transition metal cations.Rapid Commun Mass Spectrom. 23(1):31-38.
    View at Publisher | View at Google Scholar
  36. Wu et al. 2014.Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.Science 344: 58–64.
    View at Publisher | View at Google Scholar
  37. Wyttenbach T., Liu D., Bowers M.T. 2008.Interactions of the hormone oxytocin with divalent metal ions.J. Am. Chem. Soc., 130: 5993–6000.
    View at Publisher | View at Google Scholar
  38. Yoon, H.I. et al., 2016.Bioorthogonal copper-free “click” chemistry for labeling and tracking of chondrocytes in vivo.Bioconjug. Chem. 27: 927–936.
    View at Publisher | View at Google Scholar
  39. Zhang Y.S., Khadenhosseini A. 2017.Advances in engineering hydrogels.Science 356: 500.
    View at Publisher | View at Google Scholar

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad